Transcription regulation in NIH3T3 cell clones resistant to diethylmaleate-induced oxidative stress and apoptosis

Raffaella Faraonio, Paola Vergara, Domenico Di Marzo, Maria Napolitano, Tommaso Russo, Filiberto Cimino

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To investigate the molecular mechanisms underlying the induction of cell resistance to oxidative stress, NIH3T3 cell clones (NIH-DEM clones) were isolated and selected for their ability to survive the exposure to diethylmaleate (DEM), a glutathione-depleting agent. The oxidative stress-resistant phenotype of these clones is stable for at least 1 month in the absence of DEM, and includes the resistance also to other apoptosis-inducing stimuli. The expression profile of several antioxidant genes was examined in four of the DEM-resistant clones in the presence and in absence of DEM. The response to the acute exposure to DEM is similar in wild type and DEM-resistant cells, with the exception of the glutathione-S-transferase α1 gene, whose expression is highly induced in NIH-DEM clones. However, in the absence of an acute stress, the expression of some genes is higher in DEM-resistant clones than in wild-type cells and the gene expression profile significantly varies among the clones. In particular, glutathione-S-transferase α1 and cystine/glutamate transporter mRNAs are increased in NIH-DEM-12. In these cells, the promoters of the two genes drive a stronger transcription than in wild-type cells, and this appears to be dependent on the transcription factor Nrf2.

Original languageEnglish
Pages (from-to)365-374
Number of pages10
JournalAntioxidants and Redox Signaling
Issue number3-4
Publication statusPublished - Mar 2006

ASJC Scopus subject areas

  • Biochemistry


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